Sandbox 208: Difference between revisions
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= Biological role = | = Biological role = | ||
Rab-GDI does not facilitate Rab prenylation, but serves as a generic regulator for recycling of | Rab-GDI does not facilitate Rab prenylation, but serves as a generic regulator for recycling of Rab-GTPases for use in multiple rounds of membrane transport. It retrieves Rabs in the GDP-bound form from the membrane and delivers it to the cytosol, controlling the distribution of Rabs between membranes and cytosol. GDI is believed to be stably only with GDP-loaded and prenylated Rabs proteins, ensuring retrieval of inactivated Rab GTPases from the membrane at the end of their functionnal cycle. Rab-GDI is critically important for the proper functionning of the vesicular transport machinery, and its deletion can be lethal. | ||
= Structure = | = Structure = | ||
== General structure == | == General structure == | ||
== Substrate binding | == Substrate binding == | ||
== | GDI binds the Rab molecule via three interaction sites: | ||
'''GDI-Rab Binding Platform (RBP)''', located in domain I, which interacts extensively with the globular part of the Rab molecule. | |||
'''GDI C-terminus Coordinating Region (CCR)''', located in the cleft between domain I and domain II, which coordinates the flexible extended C-terminus of Rab. It is formed by residues 93-112 from domain I and 226-235 from domain II and reprent a hydrophobic cavity on the surface of the protein located between the GDI domains. Hydrophobic contacts between GDI and Rab are supported by a hydrogen bond involving main chain atoms. | |||
'''Domain II of GDI''', consisting solely of alpha helices, which form a prenyl-lipid binding pocket, exhibiting an open conformation and accomodating the prenyl moiety of a modified Rab if present. | |||
== Catalytic mechanism == | |||
= Diseases = | = Diseases = | ||